Gold nanoparticles carrying or not anti-VEGF antibody do not change glioblastoma multiforme tumor progression in mice

Author(s)

Jesus da Silva, Viviane de Cassia ^[1] ; Silva, Renee de Nazare O. ^[2] ; Colli, Lucas Giglio ^[3] ; Catelli de Carvalho, Maria Helena ^[3] ; Rodrigues, Stephen Fernandes ^{[1, 3]}

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci 1, Dept Pharmacol, Lab Vasc Nanopharmacol, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci 1, Dept Pharmacol, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci 1, Dept Pharmacol, Lab Hypertens Diabet & Vasc Biol, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: HELIYON; v. 6, n. 11 NOV 2020.
• Web of Science Citations: 0

Abstract

Aims: Glioblastoma multiforme (GBM) is the most devastating malignant primary brain tumor known. Life expectance is around 15 months after diagnosis. Several events contribute to the GBM progression such as uncontrolled genetic cancer cells proliferation, angiogenesis (mostly vascular endothelial growth factor (VEGF)mediated), tissue invasion, glioma stem cell activity, immune system failure, and a hypoxic and inflammatory tumor microenvironment. Tumor cells antiproliferative effect of 20 nm citrate-covered gold nanoparticles (cit-AuNP) has been reported, along with anti-inflammatory and anti-oxidative effects. We aimed to test whether either chronic treatment with 20 nm cit-AuNP or anti-VEGF antibody (Ig)-covered AuNP could reduce GBM progression in mice. Main methods: Effect of the gold nanoparticles on the GL261 glioblastoma cells proliferation in vitro, and on the GL261-induced glioblastoma cell growth in C57BL/6 mice in vivo were tested. Besides, fluorophore-conjugated gold nanoparticles penetration through the GL261 plasma cell membrane, gold labelling in brain parenchyma of glioblastoma-carrying mice, and VEGF expression into the tumor were evaluated. Key findings: We observed cit-AuNP did no change the GL261 cells proliferation. Similarly, we demonstrated chronic treatment with either cit-AuNP or anti-VEGF Ig-covered AuNP did not modify the GL261 cells-induced GBM progression in mice. By the end, we showed AuNPs did not trespass in appreciable amount both the GL261 plasma cell membrane and the tumoral blood brain barrier (BBB), and did not change the VEGF expression into the tumor. Significance: 20 nm cit-AuNP or anti-VEGF Ig covered-AuNP are not good tools to reduce GBM in mice, probably because they do not penetrate both tumor cells and BBB in enough amount to reduce tumor growing. (AU)

• FAPESP's process: 15/04281-0 - Therapeutical efficacy of gold nanoparticles to multiform glioblastoma or septic encephalophaty in mice
• Grantee: Stephen Fernandes de Paula Rodrigues
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 18/12368-6 - Kinesis of a fluorescently labelled gold nanoparticle through the blood brain barrier of mice, in vivo, and in the murine glioblastoma cell line, GL261
• Grantee: Viviane de Cassia Jesus da Silva
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 14/05146-6 - Therapeutical efficacy of gold nanoparticles to glioblastoma multiform or septic encephalopathy in mice
• Grantee: Stephen Fernandes de Paula Rodrigues
• Support Opportunities: Research Grants - Young Investigators Grants